CN103483117B - The manufacture method of compound - Google Patents

The manufacture method of compound Download PDF

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CN103483117B
CN103483117B CN201310224992.1A CN201310224992A CN103483117B CN 103483117 B CN103483117 B CN 103483117B CN 201310224992 A CN201310224992 A CN 201310224992A CN 103483117 B CN103483117 B CN 103483117B
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CN103483117A (en
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堀口雅弘
青木良夫
林正直
楠本哲生
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DIC Corp
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Dainippon Ink and Chemicals Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/12—Formation or introduction of functional groups containing oxygen of carboxylic acid ester groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B41/00—Formation or introduction of functional groups containing oxygen
    • C07B41/08—Formation or introduction of functional groups containing oxygen of carboxyl groups or salts, halides or anhydrides thereof
    • C07B41/10—Salts, halides or anhydrides of carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/72—Hydrazones
    • C07C251/88—Hydrazones having also the other nitrogen atom doubly-bound to a carbon atom, e.g. azines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/14—Compounds containing a carbon atom having four bonds to hetero atoms with a double bond to one hetero atom and at least one bond to a sulfur atom further doubly-bound to oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/54—Preparation of carboxylic acid anhydrides
    • C07C51/56—Preparation of carboxylic acid anhydrides from organic acids, their salts, their esters or their halides, e.g. by carboxylation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/12—Preparation of carboxylic acid esters from asymmetrical anhydrides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/84—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
    • C07C69/92—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring with etherified hydroxyl groups

Abstract

The problem to be solved in the present invention be to provide it is a kind of in high yield and the manufacture method of the few compound with ester bond and/or amido link of impurity content and the high-purity compound that is obtained by the manufacture method.The present invention provides a kind of mixed acid anhydride（4）Manufacture method, the manufacture method is not by the compound with least one carboxyl（1）And alkali（2）It is pre-mixed but at the same time to acetyl halide compound（3）Add and reacted, and a kind of ester compounds and/or amide compound are provided（6）Manufacture method, the manufacture method is not by the compound with least one carboxyl（1）And alkali（2）It is pre-mixed but at the same time to acetyl halide compound（3）Addition, is reacted and mixed acid anhydride is made（4）, then make the compound with least one group selected from hydroxyl, sulfydryl and/or amino（5）Further reaction.

Description

The manufacture method of compound
Technical field
The present invention relates to the manufacture method with ester bond and/or the compound of amido link, containing being obtained by the manufacture method The composition of the compound arrived and the pharmaceuticals of use said composition, pesticide, liquid crystal material, polymer, resin, pigment, dye Material, cosmetics, food, ink, sticker, bonding agent, printed matter, optically anisotropic body, display element and electronic equipment.
Background technology
Compound with ester bond and/or amido link is with synthetic resin, liquid crystal material, pharmaceuticals, pesticide, pigment, dye Material, food, synthetic fibers, plastics, additive or cosmetics are to be utilized in the various uses of representative.In any purposes, from From the viewpoint of quality, security and reliability, it is high-purity to require these compounds.In addition, the viewpoint from rentability Set out, it is important to manufacture these compounds with good yield.
Particularly in field of electronic materials, it is desirable to which the purity of the compound used is high.For example, in field of electronic materials Polymerizable liquid crystal material is used in optically anisotropic body field.For optically anisotropic body, make polymerizable liquid crystal Composition is polymerize after being arranged under mesomorphic state, so as to be obtained as the film with homogeneous orientation, resin.So system Film, the resin of work can be used in polarizer, polarizer needed in liquid crystal display etc..In most cases, in order to meet It is required that optical characteristics, polymerization speed, dissolubility, fusing point, glass transition temperature, the transparency of film, mechanical strength, case hardness, Heat resistance and light resistance, can be used the composition formed by polymerizable compound of more than two kinds.If however, form composition Polymerizable compound in be mixed into impurity, then film, the resin made produce sometimes it is mottled, discoloration the problems such as.If there will be spot The film refute, to change colour is used as the optical film of such as liquid crystal display, then the brightness of picture becomes uneven or display color Modulation obtains unnatural, therefore the display quality of liquid crystal display can be greatly reduced.Therefore, in the feelings for field of electronic materials Under condition, it is desirable to the impurity management of ppm ranks.
As the manufacture method with ester bond and/or the compound of amido link, it is known that various methods, but by making with carboxylic The mixed acid anhydride of the precursor of base and the manufacture method reacted in the presence of a base of precursor with hydroxyl, amino and/or sulfydryl due to The low in raw material price that reaction condition is gentle, uses, thus be widely used.However, implement to be somebody's turn to do using known reaction condition During manufacture method, the refining step for removing unreacted raw material is needed since the conversion ratio to target compound is low, is existed The problem of separation yield is lower or the purity of target compound reduces.In addition, after refined, there is also unreacted raw material, by-product The problem of thing remains.Made using the polymerizable liquid crystal compound containing such compound with ester bond and/or amido link Film can produce mottled, or discoloration can be caused after baking processing after polymerisation or after being carried out to be fully cured, will so Film be used as such as liquid crystal display component when, there is the problem of quality of product can be greatly reduced.Therefore, it is necessary to one kind The manufacture method of compound with ester bond and/or amido link can be obtained with good yield, high-purity.
Prior art literature
Patent document
Patent document 1：Japanese Unexamined Patent Publication 2011-057635 publications
Patent document 2：WO2009-122868A1 publications
Patent document 3：Japanese Unexamined Patent Publication 9-104642 publications
Non-patent literature
Non-patent literature 1：The Journal of Organic Chemistry,1991,56（1）, in 405-411 inventions Hold
Problems to be solved by the invention
The problem to be solved in the present invention be to provide it is a kind of in high yield and impurity content it is few there is ester bond and/or amido link Compound manufacture method and the high-purity compound that is obtained by the manufacture method.
The means solved the problems, such as
The present invention, which provides, a kind of to be characterized in that not being pre-mixed the compound with least one carboxyl and alkali but same When to acetyl halide compound addition and the manufacture method reacted and the high-purity compound obtained by the manufacture method, Further provide for it is a kind of using the high-purity compound as the compound and its manufacture method of intermediate and use the high purity The high-purity composition of compound.
Invention effect
There is the compound of ester bond and/or amido link due in high yield and miscellaneous by what the manufacturing method of the present invention manufactured Matter content is few thus useful as the component parts of various compositions.In addition, contain the change manufactured by manufacture method of the present invention The composition of compound is in pharmaceuticals, pesticide, liquid crystal material, polymer, resin, pigment, dyestuff, cosmetics, food, ink, viscous Useful in the purposes of agent, bonding agent, printed matter, optically anisotropic body, display element and electronic equipment.
Embodiment
The present invention provides a kind of not by the compound with least one carboxyl（1）With alkali（2）Be pre-mixed but at the same time To acetyl halide compound（3）The mixed acid anhydride for adding and being reacted（4）Manufacture method, and provide a kind of ester compounds and/ Or amide compound（6）Manufacture method, the manufacture method is not by the compound with least one carboxyl（1）With alkali（2）In advance First mix but at the same time to acetyl halide compound（3）Addition, is reacted and mixed acid anhydride is made（4）, then make have at least one The compound of a group selected from hydroxyl, sulfydryl and/or amino（5）Further reaction.
In these embodiments, there is the compound of at least one carboxyl（1）Preferably aromatic carboxylic acid or aliphatic Carboxylic acid.
Compound with least one group selected from hydroxyl, sulfydryl and/or amino（5）Preferably alcohols, phenol Class, thio-alcohol, benzenethiol class, aromatic amine and/or aliphatic amine.
Acetyl halide compound（3）Preferably sulfamic acid halide, carboxylic acid halide or halogen formate ester compounds.
Alkali（2）Preferably amine, acid amides, carbamate, acid imide, sulfonamide, guanidine, hydrazone, hydrazides, hydrazine, heterocyclic amine, they Salt, metal alkoxide or metal hydroxides.
Further, there is the compound of at least one carboxyl（1）Preferably by the following general formula（I）The compound of expression.
[chemical formula 1] R1——G1——W1（I）
（In formula, G1Represent following formula（i）,
[chemical formula 2]
（In formula, A1Isosorbide-5-Nitrae-phenylene, naphthalene -2,6- diyl, Isosorbide-5-Nitrae-cyclohexylidene, Isosorbide-5-Nitrae-Asia hexamethylene are represented independently of one another Bicyclic [2.2.2] octamethylene of alkenyl, 1,4-, decahydronaphthalenes -2,6- diyls, 1,2,3,4-tetralin -2,6- diyls, pyridine - 2,6- diyls, pyrimidine -2,5- diyl, 1,3- dioxanes -2,5- diyl or singly-bound, these groups can unsubstituted or respective independences Ground is substituted by the alkyl of halogen, cyano group, nitro, Pentafluorosulfanyl or carbon number 1 to 10, more than 1 hydrogen atom in the alkyl It can be substituted independently of one another by fluorine atom or chlorine atom, 1 on the alkyl-CH2- or non-conterminous more than 2-CH2- can be each From independently by-O- ,-S- ,-CO- ,-COO- ,-OCO- ,-CO-S- ,-S-CO- ,-O-CO-O- ,-CO-NH- ,-NH-CO- ,-CH =CH-COO- ,-CH=CH-OCO- ,-COO-CH=CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y is independently of one another Represent hydrogen atom, the alkyl of carbon number 1 to 12, fluorine atom, chlorine atom or cyano group.）Substitution, A1It can be represented by P-Sp- Group substitutes（In formula, P is represented from following formula（P-1）To formula（P-17）In the group selected,
[chemical formula 3]
Sp represents 1-CH2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-S- ,-CO- ,-COO- ,- OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-CH=CH-COO-、-CH=CH-OCO-、-COO-CH= CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y represents the alkane of hydrogen atom, carbon number 1 to 12 independently of one another Base, fluorine atom, chlorine atom or cyano group.）The alkylidene or singly-bound of substituted carbon number 1 to 20.）；Z11And Z12It is each independent Ground expression-O- ,-S- ,-OCH2-、-CH2O-、-CO-、-COO-、-OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、- NH-CO-、-SCH2-、-CH2S-、-CF2O-、-OCF2-、-CF2S-、-SCF2-、-CH2CH2-、-CH2CF2-、-CF2CH2-、- CF2CF2-、-CH=CH-COO-、-CH=CH-OCO-、-COO-CH=CH-、-OCO-CH=CH-、-COO-CH2CH2-、-OCO- CH2CH2-、-CH2CH2-COO-、-CH2CH2-OCO-、-COO-CH2-、-OCO-CH2-、-CH2-COO-、-CH2-OCO-、-CY= CY-（In formula, Y represents hydrogen atom, the alkyl of carbon number 1 to 12, fluorine atom, chlorine atom or cyano group independently of one another.）、-C≡ The alkylidene or singly-bound of C- ,-CH=N- ,-N=CH- ,-N=N- ,-CH=N-N=CH-, carbon number 1 to 20,1 in the alkylidene Above hydrogen atom can be substituted by fluorine atom or chlorine atom independently of one another, 1 on the alkylidene-CH2- or it is 2 non-conterminous - CH above2- can be independently of one another by-O- ,-S- ,-CO- ,-COO- ,-OCO- ,-CO-S- ,-S-CO- ,-O-CO-O- ,-CO- NH- ,-NH-CO- ,-CH=CH-COO- ,-CH=CH-OCO- ,-COO-CH=CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C- （In formula, Y represents hydrogen atom, the alkyl of carbon number 1 to 12, fluorine atom, chlorine atom or cyano group independently of one another.）Substitution, m11 Represent 0 to 8 integer.）；R1And W1Hydrogen atom, fluorine atom, chlorine atom, bromine atoms, iodine atom, five fluorine are represented independently of one another Sulfanyl, cyano group, nitro, the alkyl or P-Sp- of carbon number 1 to 20（In formula, P is represented and A1In the identical implications of P, Sp Expression and A1In the identical implications of Sp, but can be that identical group can also be different groups.）, in the alkyl 1 with Upper hydrogen atom can be substituted by fluorine atom or chlorine atom independently of one another, 1 on the alkyl-CH2- or more than 2 non-conterminous- CH2- can independently of one another by-O- ,-S- ,-CO- ,-COO- ,-OCO- ,-CO-S- ,-S-CO- ,-O-CO-O- ,-CO-NH- ,- NH-CO- ,-CH=CH-COO- ,-CH=CH-OCO- ,-COO-CH=CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y Hydrogen atom, the alkyl of carbon number 1 to 12, fluorine atom, chlorine atom or cyano group are represented independently of one another.）Substitution, R1And W1In At least one expression carboxyl.）
Further, there is the compound of at least one group selected from hydroxyl, sulfydryl and/or amino（5）Preferably By following formula（II）The compound of expression.
[chemical formula 4] R2——G2——W2（II）
（In formula, G2Represent following formula（ii）,
[chemical formula 5]
（In formula, A21,4- phenylenes, naphthalene -2,6- diyls, 1,4- cyclohexylidenes, 1,4- Asias hexamethylene are represented independently of one another Bicyclic [2.2.2] octamethylene of alkenyl, 1,4-, decahydronaphthalenes -2,6- diyls, 1,2,3,4-tetralin -2,6- diyls, pyridine - 2,6- diyls, pyrimidine -2,5- diyl, 1,3- dioxanes -2,5- diyl or singly-bound, these groups can unsubstituted or respective independences Ground is substituted by the alkyl of halogen, cyano group, nitro, Pentafluorosulfanyl or carbon number 1 to 10, more than 1 hydrogen atom in the alkyl It can be substituted independently of one another by fluorine atom or chlorine atom, 1 on the alkyl-CH2- or non-conterminous more than 2-CH2- can be each From independently by-O- ,-S- ,-CO- ,-COO- ,-OCO- ,-CO-S- ,-S-CO- ,-O-CO-O- ,-CO-NH- ,-NH-CO- ,-CH =CH-COO- ,-CH=CH-OCO- ,-COO-CH=CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y is independently of one another Represent hydrogen atom, the alkyl of carbon number 1 to 12, fluorine atom, chlorine atom or cyano group.）Substitution, A2Can be by by P-Sp-（In formula, P Expression and A1In the identical implications of P, Sp is represented and A1In the identical implications of Sp, but can be that identical group can also be Different groups.）The group substitution of expression；Z21And Z22Expression-O- ,-S- ,-OCH independently of one another2-、-CH2O-、-CO-、- COO-、-OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-SCH2-、-CH2S-、-CF2O-、- OCF2-、-CF2S-、-SCF2-、-CH2CH2-、-CH2CF2-、-CF2CH2-、-CF2CF2-、-CH=CH-COO-、-CH=CH-OCO-、- COO-CH=CH-、-OCO-CH=CH-、-COO-CH2CH2-、-OCO-CH2CH2-、-CH2CH2-COO-、-CH2CH2-OCO-、-COO- CH2-、-OCO-CH2-、-CH2-COO-、-CH2-OCO-、-CY=CY-（In formula, Y represents hydrogen atom, carbon number independently of one another 1 to 12 alkyl, fluorine atom, chlorine atom or cyano group.）,-C ≡ C- ,-CH=N- ,-N=CH- ,-N=N- ,-CH=N-N=CH-, carbon it is former The alkylidene or singly-bound of subnumber 1 to 20, more than 1 hydrogen atom can be taken by fluorine atom or chlorine atom independently of one another in the alkylidene Generation, 1-CH on the alkylidene2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-S- ,-CO- ,- COO-、-OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-CH=CH-COO-、-CH=CH-OCO-、- COO-CH=CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y represent independently of one another hydrogen atom, carbon number 1 to 12 alkyl, fluorine atom, chlorine atom or cyano group.）Substitution, m21 represent 0 to 8 integer.）；R2And W2Represent independently of one another Hydrogen atom, fluorine atom, chlorine atom, bromine atoms, iodine atom, Pentafluorosulfanyl, cyano group, nitro, carbon number 1 to 20 alkyl or P-Sp-（In formula, P is represented and A1In the identical implications of P, Sp is represented and A1In the identical implications of Sp, but can be identical Group can also be different groups.）, more than 1 hydrogen atom can be taken by fluorine atom or chlorine atom independently of one another in the alkyl Generation, 1-CH on the alkyl2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-S- ,-CO- ,-COO- ,- OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-CH=CH-COO-、-CH=CH-OCO-、-COO-CH= CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y represents the alkane of hydrogen atom, carbon number 1 to 12 independently of one another Base, fluorine atom, chlorine atom or cyano group.）Substitution, R2And W2In at least one expression selected from hydroxyl, sulfydryl and/or amino The group gone out.）
Further, acetyl halide compound（3）Preferably by following formula（III-1）Or formula（III-2）The compound of expression.
[chemical formula 5]
（In formula, U1Represent organic group, U2Represent hydrogen atom or organic group, V represents halogen.）
Mixed acid anhydride（4）Preferably by the following general formula（IV）The compound of expression.
[chemical formula 6] R3——G3——W3（IV）
（In formula, R3、G3And W3Expression and general formula respectively（I）In R1、G1And W1Identical implication, but in general formula（I） Middle R1And/or W1In the case of representing carboxyl, corresponding R3And/or W3By following formula（IV-1）Or formula（IV-2）Represent.
[chemical formula 7]
（In formula, U1And U2Expression and formula（III-1）And formula（III-2）In U1And U2Identical implication.））
Ester compounds and/or amide compound（6）Preferably by the following general formula（V-1）To general formula（V-3）The chemical combination of expression Thing.
[chemical formula 8]
R4——G1——Q1——G2——W4 (V-1)
R4——G1——Q1——G2——Q2——G1——W4 (V-2)
R4——G2——Q1——Gl——Q2——G2——W4 (V-3)
（In formula, G1Expression and general formula（I）In G1Identical implication, G2Expression and general formula（II）In G2Identical contains Justice, Q1And Q2Expression-COO- ,-OCO- ,-CONH- ,-NHCO- ,-COS- or-SCO-, R independently of one another4And W4Each solely On the spot expression and general formula（I）In R1Or W1Or general formula（II）In R2Or W2Identical implication.）Passed through by the P groups represented Radical polymerization, radical addition polymerization, cationic polymerization and anionic polymerisation and cure.Especially as polymerization And in the case of carrying out polymerizable ultraviolet, preferred formula（P-1）, formula（P-2）, formula（P-3）, formula（P-4）, formula（P-5）, formula（P-7）、 Formula（P-11）, formula（P-13）Or formula（P-15）, more preferably formula（P-1）, formula（P-2）, formula（P-7）, formula（P-11）Or formula（P-13）, Particularly preferred formula（P-1）Or formula（P-2）.
Sp represents 1-CH2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-S- ,-CO- ,-COO- ,- OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-CH=CH-COO-、-CH=CH-OCO-、-COO-CH= CH- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y represents the alkane of hydrogen atom, carbon number 1 to 12 independently of one another Base, fluorine atom, chlorine atom or cyano group.）The alkylidene or singly-bound of substituted carbon number 1 to 20, but will be manufactured by the present invention Method manufacture compound be used for liquid crystal material in the case of, from liquid crystal liquid crystal property and with from the viewpoint of the intermiscibility of other compositions, It is preferred that 1-CH2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-COO- ,-OCO- ,-O-CO-O- ,-CH= CH-COO- ,-OCO-CH=CH- ,-CY=CY- or-C ≡ C-（In formula, Y represents hydrogen atom, carbon number 1 to 12 independently of one another Alkyl.）The alkylidene or singly-bound of substituted carbon number 1 to 12, more preferably 1-CH2- or non-conterminous more than 2-CH2- Can independently of one another by-O- ,-COO- or-OCO- substitution carbon number 1 to 12 alkylidene or singly-bound, particularly preferred 1- CH2- or non-conterminous more than 2-CH2- can be independently of one another by the Asia of the carbon number 1 to 8 of-O- ,-COO- or-OCO- substitution Alkyl or singly-bound.
Further, by general formula（I）And general formula（II）In the compound of expression, from the viewpoint of synthesis easily and use In the case of liquid crystal material from the viewpoint of liquid crystal liquid crystal property, preferably A1And A2To be unsubstituted independently of one another or can be each only On the spot by cyano group, nitro substitutes, more than 1 hydrogen atom can be substituted independently of one another by fluorine atom or chlorine atom, and/or the alkyl On 1-CH2- or non-conterminous more than 2-CH2- can be substituted independently of one another by-O- ,-S- ,-CO- ,-COO- ,-OCO- The alkyl of carbon number 1 to 10, or for can by Isosorbide-5-Nitrae-phenylene that the group represented by P-Sp- substitutes, naphthalene -2,6- diyl, Bicyclic [2.2.2] octamethylene of 1,4- cyclohexylidenes, 1,4- cyclohexadienylidenes, 1,4-, decahydronaphthalenes -2,6- diyls, 1,2,3,4- Tetrahydronaphthalene -2,6- diyl, pyridine -2,6- diyl, pyrimidine -2,5- diyl, the situation of 1,3- dioxane -2,5- diyls, it is more excellent Elect as it is unsubstituted independently of one another or can independently of one another by cyano group, nitro substitute, more than 1 hydrogen atom can independently of one another by 1-CH on fluorine atom or chlorine atom substitution, and/or the alkyl2- or non-conterminous more than 2-CH2- can be independently of one another By alkyl-substituted 1,4- phenylenes, the naphthalene -2,6- two of-O-,-S-,-CO-,-COO-,-the OCO- carbon number 1 to 10 substituted The situation of base, Isosorbide-5-Nitrae-cyclohexylidene, particularly preferably unsubstituted independently of one another or more than 1 hydrogen atom can independently of one another by 1-CH in fluorine atom substitution, and/or the alkyl2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,- The alkyl-substituted 1,4- phenylenes for the carbon number 1 to 10 that S-,-CO-,-COO-,-OCO- substitute, the feelings of naphthalene -2,6- diyls Condition,
Z11、Z12、Z21And Z22It is preferred that it is each independently-O- ,-S- ,-OCH2-、-CH2O-、-CO-、-COO-、- OCO-、-CO-S-、-S-CO-、-O-CO-O-、-CO-NH-、-NH-CO-、-SCH2-、-CH2S-、-CF2O-、-OCF2-、- CF2S-、-SCF2-、-CH2CH2-、-CH2CF2-、-CF2CH2-、-CF2CF2-、-CH=CH-COO-、-OCO-CH=CH-、-COO- CH2CH2-、-OCO-CH2CH2-、-CH2CH2-COO-、-CH2CH2-OCO-、-CY=CY-（In formula, Y represents hydrogen original independently of one another Son, the alkyl of carbon number 1 to 12.）,-C ≡ C- ,-CH=N- ,-N=CH- ,-N=N- ,-CH=N-N=CH-, more than 1 hydrogen atom It can be substituted independently of one another by fluorine atom or chlorine atom and/or 1-CH2- or non-conterminous more than 2-CH2- can be each independent Ground by-O- ,-S- ,-COO- ,-OCO- substitution carbon number 1 to 20 alkylidene or singly-bound, more preferably each independently for- O-、-S-、-OCH2-、-CH2O-、-COO-、-OCO-、-CH2CH2-、-CH=CH-COO-、-OCO-CH=CH-、-COO- CH2CH2-、-OCO-CH2CH2-、-CH2CH2-COO-、-CH2CH2-OCO-、-CY=CY-（In formula, Y represents hydrogen original independently of one another Son, the alkyl of carbon number 1 to 12.）,-C ≡ C- ,-CH=N- ,-N=CH- ,-N=N- ,-CH=N-N=CH-, more than 1 hydrogen atom The alkylidene or singly-bound for the carbon number 1 to 20 that can be replaced by fluorine atoms independently of one another,
It is preferred that m11 and m21 are each independently the situation of 1 to 5 integer, the situation of more preferably 1 to 3 integer, Particularly preferably 1 or 2 situation,
It is preferred that R1And W1R independently of one another1And W1In two represent carboxyls or R1And W1In one expression Carboxyl, another represents that hydrogen atom, fluorine atom, chlorine atom, cyano group or more than 1 hydrogen atom can be independently of one another by fluorine atoms Or chlorine atom substitution, and/or 1-CH2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-S- ,-COO- ,- The alkyl or R of the carbon number 1 to 20 of OCO- substitutions1And W1Represent by the situation of the P-Sp- groups represented, more preferably R1With And W1In two represent carboxyls or R1And W1In an expression carboxyl, another represents hydrogen atom, fluorine atom or 1 The alkyl or R for the carbon number 1 to 12 that above hydrogen atom can be replaced by fluorine atoms independently of one another1And W1Represent by P-Sp- The situation of the group of expression,
It is preferred that R2And W2R independently of one another2And W2In two represent to select from hydroxyl, sulfydryl and/or amino Group, or R2And W2In a group for representing to select from hydroxyl, sulfydryl and/or amino, another represent that hydrogen is former Son, fluorine atom, chlorine atom, cyano group or more than 1 hydrogen atom can be substituted by fluorine atom or chlorine atom, and/or 1 independently of one another A-CH2- or non-conterminous more than 2-CH2- the carbon number 1 that can be substituted independently of one another by-O- ,-S- ,-COO- ,-OCO- To 20 alkyl, or R2And W2Represent by the situation of the P-Sp- groups represented, more preferably R2And W2In two expression Hydroxyl, or R2And W2In one represent hydroxyl, another represent that hydrogen atom, fluorine atom or more than 1 hydrogen atom can be each From the alkyl for the carbon number 1 to 12 being independently replaced by fluorine atoms, or R2And W2Represent by the feelings of the P-Sp- groups represented Condition,
In R1And W1Two represent carboxyls in the case of, preferably R2And W2Only one represent from hydroxyl, sulfydryl And/or the situation for the group selected in amino, more preferably R2And W2Only one represent hydroxyl situation,
In R2And W2Two represent under the feelings of group selected from hydroxyl, sulfydryl and/or amino, preferably R1And W1Only one represent carboxyl situation.
Specific embodiment is recorded further below, but in order to simplify, by the chemical combination with least one carboxyl Thing（1）Carboxylic acid is denoted as, by the compound with least one group selected from hydroxyl, sulfydryl and/or amino（4）It is denoted as parent Core reagent.
Acetyl halide compound（3）Preferably sulfamic acid halide or carboxylic acid halide, preferably by anti-with carboxylic acid in the presence of a base Answer and generate the carboxylic acid derivates with detachment substituent, further reacted by the carboxylic acid derivates and nucleopilic reagent to make The material that the substituent efficiency of detachment departs from well.As the acetyl halide compound being readily available, for example, first sulphur Acyl chlorides, toluene sulfochloride, chloroacetic chloride etc..
The acetyl halide compound used（3）Amount be not particularly limited, but relative to carboxylic acid be less than 1 equivalent in the case of, It is unreacted carboxylic acid remained after reaction.Therefore, it is necessary to pass through the unreacted carboxylic acid of refined removing after reaction.In general, it can pass through The methods of column chromatography, recrystallization, reprecipitation, distillation, distillation, removes carboxylic acid.On the other hand, acetyl halide compound amount relative to In the case that carboxylic acid is more than 1 equivalent, acetyl halide compound remains after reaction.In this case also can be by same method come smart System.It is 0.1~10 equivalent preferably with respect to carboxylic acid, more preferably 0.5~2 equivalent from the viewpoint of easily refining, further Preferably 0.8~1.5 equivalent.
Alkali（2）Preferably amine, acid amides, carbamate, acid imide, sulfonamide, guanidine, hydrazone, hydrazides, hydrazine, heterocyclic amine, they Salt, metal alkoxide or metal hydroxides, but from the viewpoint of yield, more preferably tertiary amine or aromatic amine and its amine salt. As the alkali being readily available, for example, triethylamine, N, N- dimethyl amines, N, N- diethyl methyl amines, triethylamine, N, N- Dimethyl propylamine, N, N- dimethyl butylamines, N, N- dimethylamylamines, N, N- diethyl propylamine, N, N- dipropyl ethamine, N, N- bis- Propyl methylamine, N, N- diethyl amylamine, N- ethyl-N-methyls amylamine, tri-n-butylamine, N, N- dibutylmethylamines, N, N- dibutyl second Amine, N, N- dibutyl propylamine, N- ethyl-N-methyls propylamine, N, N- dipropyl methylamine, N are N- dipropyl ethamine, tripropyl amine (TPA), three different Propylamine, N- methyl diisopropylamine, N- ethyl diisopropylamines, N- propyl group diisopropylamine, N- butyl diisopropylamine, pyridine, N- methyl Pyridine, 2- chloropyridines, 2- bromopyridines, piperidines, pyrimidine, quinoline, acridine, N, N- dimethyl -4-aminopyridine, picoline, connection Pyridine, 2,6- lutidines, pyridinium chloro-chromate, pyridinium p-toluenesulfonate etc..One kind can be used only in alkali, can also Use more than two kinds.In addition, implementing to add and carry out anti-to acetyl halide compound comprising not being pre-mixed carboxylic acid and alkali , can be by alkali only in the first step in the case of the process and the manufacture method for the process for reacting nucleopilic reagent answered（By with extremely The compound of a few carboxyl（1）, alkali（2）And acetyl halide compound（3）Obtain mixed acid anhydride（4）Process）Middle use, or Also can be in the first step and the second step（By mixed acid anhydride（4）And with least one from hydroxyl, sulfydryl and/or amino In the compound of group selected（5）Obtain ester compounds and/or amide compound（6）Process）Both in use.
The reaction temperature of the first step and the second step is all usually -50 DEG C to 150 DEG C, but in the situation using solvent Lower is -50 DEG C of reflux temperatures to solvent.Preferably -50 DEG C to 60 DEG C from the viewpoint of yield, from the sight of the efficiency of operation Point sets out more preferably -10 DEG C to 40 DEG C.
Acetyl halide compound（3）It can directly use, can also be dissolved in solvent and be used as solution, can also be suspended in Use as suspension in solvent, but used from the viewpoint of yield and reaction controlling preferably as solution or suspension.
Carboxylic acid, alkali（2）And nucleopilic reagent can be used directly respectively, be also dissolvable in water in solvent used as solution, also It can be suspended in solvent and be used as suspension, but preferably as solution or suspension from the viewpoint of yield and reaction controlling Liquid uses, and is used more preferably as solution.
The first step for not being pre-mixed but adding and being reacted to acetyl halide compound carboxylic acid and alkali can be under State chemical formula expression.
（Carboxylic acid）+k（Acetyl halide compound）+k（Alkali）→（Mixed acid anhydride）+k（Salt）
（In formula, k represents the equivalents for the required acetyl halide compound of 1 equivalent of carboxylic acid and alkali.）From the sight of yield Point sets out, and preferably carboxylic acid is not mixed with alkali but added at the same time, the speed of dripping of carboxylic bronsted lowry acids and bases bronsted lowry is preferably
（The speed of dripping of carboxylic acid）：（The speed of dripping of alkali）=k：1.
As the mixed acid anhydride obtained by the first step（4）It can be separated, can not also separate and be directly used in the second step. Carry out it is separated in the case of, can be post-processed and be refined by usual way.From the sight of yield and operating efficiency Point sets out, and does not preferably separate and is directly used in the one pot reaction of the second step.
The second step that nucleopilic reagent reacts is set to be represented by following chemical formula.
（Mixed acid anhydride）+l（Nucleopilic reagent）+l（Alkali）→（Object）+l（Salt）
（In formula, l represents the equivalents for the required nucleopilic reagent of 1 equivalent of mixed acid anhydride and alkali.）The first step And the equivalent of required alkali is relative to carboxylic acid in the second step（k+l）Times.In the case where being reacted in one pot, It can be added in the first step（k+l）The alkali of equivalent, the alkali of k equivalents can be also added in the first step and is added in the second step Enter the alkali of l equivalents.In addition, the equivalent of alkali can be the amount needed in theory, can also be excessive or a large amount of excessive on a small quantity.From yield And from the viewpoint of economy, the amount of alkali is a small amount of excessive preferably with respect to the amount needed in theory.
The reaction time of the first step and the second step both depends on compound, but usually a few minutes~several days, excellent Dozens of minutes is elected as to a few houres.
As the reaction dissolvent of the first step and the second step, do not have then as long as obtaining target compound during the reaction There is special limitation, as preferable reaction dissolvent, for example, chloroform, carbon tetrachloride, dichloromethane, 1,2-, bis- chloroethenes Alkane, 1,2- dichloroethylene, 1,1,2,2- tetrachloroethanes, trichloro ethylene, 1-chlorobutane, carbon disulfide, acetone, acetonitrile, benzonitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide, diethyl ether, ethylene glycol monoethyl ether, ethylene glycol monoethyl ether second Acid esters, ethylene glycol monobutyl ether, glycol monoethyl ether, diethylene glycol diethyl ether, o-dichlorohenzene, dimethylbenzene, ortho-xylene, to diformazan Benzene, meta-xylene, chlorobenzene, isobutyl acetate, isopropyl acetate, isoamyl acetate, ethyl acetate, butyl acetate, propyl acetate, Pentyl acetate, methyl acetate, 2-Methoxyethyl acetate, hexamethylphosphoric triamide, three（Dimethylamino）Phosphine, cyclohexanone, 1,4- dioxanes, styrene, tetrachloro-ethylene, tetrahydrofuran, pyridine, 1-Methyl-2-Pyrrolidone, 1,1,1- trichloroethanes, first Benzene, hexane, pentane, hexamethylene, pentamethylene, heptane, benzene, methyl iso-butyl ketone (MIBK), t-butyl methyl ether, methyl ethyl ketone, methyl ring Hexanone, methyl butyl ketone, metacetone, gasoline, coal tar naphtha, petroleum ether（petroleum ether）, naphtha, benzin （petroleum benzin）, turpentine oil, mineral spirits.From the viewpoint of compound dissolubility, preferably chloroform, dichloromethane Alkane, 1,2- dichloroethanes, acetone, acetonitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide, diethyl ether, Ethylene glycol monoethyl ether, ethyl acetate, butyl acetate, 1,4- dioxanes, tetrahydrofuran, 1-Methyl-2-Pyrrolidone, toluene, uncle Butyl methyl ether, methyl ethyl ketone.
Embodiment
Hereinafter, enumerate embodiment and further describe the present invention, but the present invention is not limited to these embodiments.It is in addition, following Embodiment and comparative example composition in " % " expression " quality % ".
The purity of compound is analyzed by GC or HPLC.Analysis condition is as follows.
（GC analysis conditions）
Column：J＆W DB-1,30m × 0.25mm × 0.25 μm
Temperature program(me)：100℃（1 minute）-（10 DEG C/min）-300℃（12 minutes）
Inlet temperature：300℃
Detector temperature：300℃
（HPLC analysis conditions）
Column：Inertsil ODS-3,5 μm,
Dissolution solvent：Acetonitrile/water（90：10）
Flow velocity：0.5mL/min
Detector：UV, 210nm
Column oven：40℃
（Embodiment 1）By formula（I-1）The compound of expression（The compound that patent document 3 is recorded）Manufacture
[chemical formula 6]
Ethyl chloroformate 5.00g is added in the reaction vessel with agitating device, thermometer and 2 dropping funels （46 mMs）And tetrahydrofuran 25mL.By acetic acid 2.77g while ice cooling（46 mMs）Tetrahydrofuran solution 10mL and tri-n-butylamine 10.2g（55 mMs）Tetrahydrofuran solution 20mL respectively from different dropping funels with（Acetic acid is molten Liquid）：（Tri-n-butylamine solution）=1：2 speed of dripping is dripped at the same time.After being stirred 30 minutes under ice cooling, carried out using dichloromethane Liquid separation handles and distills solvent, so as to obtain by formula（I-1）The compound 7.16g of expression.Yield is 98%, and purity is 99.97%.Measure gained compound1H NMR、13C NMR and mass spectrographic result and the method institute using the record of patent document 3 The determination data for obtaining compound is consistent.
（Comparative example 1）The preparation method that patent document 3 is recorded
In the reaction vessel with agitating device, thermometer and dropping funel, ethyl chloroformate 5.00g is added（46 MM）And tetrahydrofuran 25mL.Will be by acetic acid 2.77g while being cooled to -10 DEG C（46 mMs）Tri-n-butylamine 10.2g（55 mMs）And the solution of tetrahydrofuran 20mL compositions drips below 0 DEG C.Stir 30 minutes under ice-cooling Afterwards, carry out liquid separation processing using dichloromethane and distill solvent, so as to obtain by formula（I-1）The compound of expression.Yield is 92%, purity 99.89%.
（Embodiment 2）By formula（I-2）The compound of expression（The compound that patent document 3 is recorded）Manufacture
[chemical formula 7]
Mesyl chloride 15.0g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （0.13 mole）And tetrahydrofuran 30mL.Will be by formula while ice cooling（I-2-1）The compound 34.6g of expression（0.13 Mole）Tetrahydrofuran solution 200mL and tri-n-butylamine 28.9g（0.16 mole）Tetrahydrofuran solution 100mL respectively never With dripping device with（By formula（I-2-1）The solution of the compound of expression）：（Tri-n-butylamine solution）=2：1 drips speed at the same time Drip.After when stirring 1 is small while ice cooling, carries out liquid separation processing using dichloromethane and distill solvent, so as to obtain By formula（I-2）The compound 43.9g of expression.Yield is 98%, purity 95.53%.Measure gained compound1H NMR、13C NMR and mass spectrographic result are consistent with the determination data of compound obtained by the method recorded using patent document 3.
（Comparative example 2）
With reaction scale similarly to Example 2, by being manufactured with the same method of comparative example 1 by formula（I-2）Represent Compound.Yield is 94%, purity 95.50%.
（Embodiment 3）By formula（I-3）The manufacture of the compound of expression
[chemical formula 8]
Mesyl chloride 5.00g is added in the reaction unit with agitating device, thermometer and 2 dripping devices （43.6 mMs）And tetrahydrofuran 10mL.Will be by formula while ice cooling（I-3-1）The compound 12.9g of expression （44.1 mMs）Tetrahydrofuran solution 60mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 30mL points Not from different dripping devices with（By formula（I-3-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 speed of dripping Degree drips at the same time.After when stirring 1 is small while ice cooling, 4-dimethylaminopyridine 2.64g is added（21.6 mMs）With And 2-（4- hydroxyphenyls）Ethanol 2.69g（19.4 mMs）.By triethylamine 5.25g while ice cooling（51.9 mMs）Drop Under.Stir 7 it is small when after, distill solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.By organic layer saline solution After washing and neutralizing, column chromatography is utilized（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-3） The compound 12.2g of expression.Yield is 82%, purity 99.63%.
1H NMR（CDCl3）δ1.45-1.54（M, 8H）, 1.72（M, 4H）, 1.83（M, 4H）, 3.08（T, 2H）, 4.03 （Quin, 4H）, 4.18（Quin, 4H）, 4.51（T, 2H）, 5.83（D, 2H）, 6.13（Dd, 2H）, 6.38（D, 2H）, 6.89（D, 2H）, 6.96（D, 2H）, 7.15（D, 2H）, 7.32（D, 2H）, 7.96（D, 2H）, 8.13（D, 2H）ppm.
LRMS（EI）m/z686（100）.
（Comparative example 3~6）
Reagent adding methods in the first step are only changed to by following methods with reaction scale similarly to Example 3, Manufacture is by formula（I-3）The compound of expression.
The Reagent adding methods of comparative example 3：To being mixed with mesyl chloride and by formula（I-3-1）The tetrahydrochysene of the compound of expression Tetrahydrofuran solution drips the tetrahydrofuran solution of triethylamine.
The Reagent adding methods of comparative example 4：Drip to the tetrahydrofuran solution of triethylamine and be mixed with mesyl chloride and by formula （I-3-1）The tetrahydrofuran solution of the compound of expression.
The Reagent adding methods of comparative example 5：To the tetrahydrofuran solution of mesyl chloride drip triethylamine tetrahydrofuran it is molten Liquid, then, drips by formula（I-3-1）The tetrahydrofuran solution of the compound of expression.
The Reagent adding methods of comparative example 6：Drip to the tetrahydrofuran solution of mesyl chloride and be mixed with triethylamine and by formula （I-3-1）The tetrahydrofuran solution of the compound of expression.
Show the result in table 1.
[table 1]
[chemical formula 9]
（Embodiment 4）By formula（I-4）The manufacture of the compound of expression
[chemical formula 10]
Will be by formula except in embodiment 3（I-3-1）The compound of expression is replaced with by formula（I-4-1）The compound of expression In addition, manufactured using method similarly to Example 3 by formula（I-4）The compound of expression.Yield is 79%, purity 99.55%.
1H NMR（DMSO-d6）δ2.11（M, 4H）, 3.05（T, 2H）, 4.15（T, 2H）, 4.18（T, 2H）, 4.28（M, 4H）, 4.46（T, 2H）, 5.96（D, 2H）, 6.19（Dd, 2H）, 6.32（D, 2H）, 7.04（D, 2H）, 7.12（D, 2H）, 7.19 （D, 2H）, 7.39（D, 2H）, 7.88（D, 2H）, 8.06（D, 2H）ppm.
13C NMR（DMSO-d6）δ 28.3,34.2,61.5,65.1,65.3,114.9,115.1,121.5,122.2, 122.4,128.7,130.3,131.6,132.0,132.0,132.4,136.2,149.7,162.8,163.5,164.6, 165.7,165.9ppm.
LRMS（EI）m/z602（100）.
（Comparative example 7）
Only the Adding Way of reagent in the first step is changed to mesyl chloride with reaction scale similarly to Example 4 Tetrahydrofuran solution drip and be mixed with triethylamine and by formula（I-4-1）The method of the tetrahydrofuran solution of the compound of expression, Manufacture is by formula（I-4）The compound of expression.Yield is 76%, purity 99.05%.
（Embodiment 5）By formula（I-5）The manufacture of the compound of expression
[chemical formula 11]
Using method similarly to Example 4, modulation contains by formula（I-4-2）The reaction solution of the compound of expression.That is, exist Mesyl chloride 5.00g is added in reaction unit with agitating device, thermometer and 2 dripping devices（43.6 mMs）With And tetrahydrofuran 10mL.Will be by formula while ice cooling（I-4-1）The compound 11.0g of expression（44.1 mMs）Tetrahydrochysene Tetrahydrofuran solution 50mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 25mL respectively from different dripping devices With（By formula（I-4-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time.
Then after when stirring 1 is small while ice cooling, 4-dimethylaminopyridine 0.53g is added（4.3 mM）With And methylnaphthohydroquinone 2.68g（21.6 mMs）.By triethylamine 5.25g while ice cooling（51.9 mMs）Drip.Stirring 1 After hour, solvent is distilled, dichloromethane is added and 5% hydrochloric acid carries out liquid separation processing.By organic layer brine It and in With it is rear, utilize column chromatography（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-5）The change of expression Compound 12.3g.Yield is 97%, purity 99.73%.
1H NMR（CDCl3）δ2.22（M, 7H）, 4.17（T, 4H）, 4.39（T, 4H）, 5.85（D, 2H）, 6.14（Dd, 2H）, 6.43（D, 2H）, 6.99（Dd, 4H）, 7.08（Dd, 1H）, 7.14（D, 1H）, 7.18（D, 1H）, 8.16（Dd, 4H）ppm.
13C NMR（CDCl3）δ 16.4,28.5,61.6,64.6,114.2,114.3,120.0,121.7,121.9, 122.9,124.1,128.2,131.0,131.7,132.3,147.0,148.4,163.0,163.1,164.4,164.8, 166.1ppm.
LRMS（EI）m/z588（100）.
（Comparative example 8）
Only the Adding Way of reagent in the first step is changed to mesyl chloride with reaction scale similarly to Example 5 Tetrahydrofuran solution drip and be mixed with triethylamine and by formula（I-4-1）The method of the tetrahydrofuran solution of the compound of expression, Manufacture is by formula（I-5）The compound of expression.Yield is 93%, purity 99.65%.
（Embodiment 6）By formula（I-6）The manufacture of the compound of expression
[chemical formula 12]
Mesyl chloride 5.00g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （43.6 mMs）And tetrahydrofuran 10mL.By 4-ABA 7.95g while ice cooling（44.1 mmoles You）Tetrahydrofuran solution 50mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 25mL respectively from difference Dripping device with（The solution of 4-ABA）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time.In ice After being stirred 30 minutes while cooling, 4-dimethylaminopyridine 0.53g is added（4.3 mM）And 2,4- xylenols 5.32g（43.6 mMs）.Drip triethylamine 5.25g while ice cooling（51.9 mMs）.Stir 1 it is small when after, distillation Fall solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.After organic layer brine It and neutralization, column is utilized Chromatography（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-6-2）The compound 12.0g of expression （42.2 mMs）.Yield is 97%, purity 99.85%.
Added in the reaction vessel with agitating device and dripping device by formula（I-6-2）The compound of expression 12.0g（42.2 mMs）, it is dissolved in toluene 20mL and tetrahydrofuran 20mL.Drip butylamine 4.62g（63.3 mMs）, When stirring 7 is small at room temperature.After being carried out liquid separation with 5% hydrochloric acid and saline solution and carried out carrying out washing treatment, pass through recrystallization（Methanol/ Water）Refined, obtained by formula（I-6-3）The compound 10.0g of expression（41.3 mMs）.
Added in the reaction vessel with agitating device, thermometer and dripping device by formula（I-6-3）The change of expression Compound 10.0g（41.3 mMs）, by formula（I-4-1）The compound 10.3g of expression（41.3 mMs）And 4- dimethylaminos Yl pyridines 0.50g（4.1 mM）, it is suspended in dichloromethane 50mL.By N, N '-diisopropyl carbon two while ice cooling Imines 6.25g（49.5 mMs）Drip in a manner of reaction temperature is no more than 15 DEG C.Be stirred at room temperature 5 it is small when after, distillation Fall solvent, utilize column chromatography（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-6）Represent Compound 16.9g（35.5 mMs）.
1H NMR（CDCl3）δ 2.19~2.25（M, 5H）, 2.34（S, 3H）, 4.17（T, 2H）, 4.39（T, 2H）, 5.85 （Dd, 1H）, 6.14（Dd, 1H）, 6.42（Dd, 1H）, 6.98~7.08（M, 5H）, 7.36（D, 2H）, 8.16（D, 2H）, 8.29 （D, 2H）ppm.
13C NMR（CDCl3）δ 16.1,20.8,28.5,61.1,64.7,113.1,114.3,121.3,121.6,122.0, 127.0,127.5,128.2,129.8,131.0,131.7,131.8,132.4,135.6,147.2,155.2,163.3, 164.2,164.3,166.1ppm.
LRMS（EI）m/z474（100）
（Comparative example 9）
Only the Adding Way of reagent in the first step is changed to mesyl chloride with reaction scale similarly to Example 6 Tetrahydrofuran solution drip the method for the tetrahydrofuran solution for being mixed with triethylamine and 4-ABA, manufacture by formula （I-6-2）The compound of expression.Yield is 94%, purity 99.68%.
Then, manufactured by method similarly to Example 6 by formula（I-6）The compound of expression.
（Embodiment 7）By formula（I-7）The compound of expression（The compound that academic documents 1 are recorded）Manufacture
[chemical formula 13]
The method recorded by academic documents 1 is manufactured by formula（I-7-1）The compound of expression.
Methylchloroformate 11.6mL is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （150 mMs）And dichloromethane 50mL.Will be by formula while ice cooling（I-7-1）The compound 14g of expression（75.2 millis Mole）Tetrahydrofuran solution 50mL and triethylamine 21mL（150 mMs）Tetrahydrofuran solution 25mL respectively from difference Dripping device with（By formula（I-7-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time Under.After when stirring 2 is small while ice cooling, solvent is distilled.By suspending, filtering and being concentrated to give by formula in diethyl ether （I-7-2）The compound 17.1g of expression（69.9 mMs）.
Obtained by use by formula（I-7-2）The compound 17.1g of expression（69.9 mMs）Recorded using academic documents 1 Method is reduced, and is obtained by formula（I-7）The compound 7.82g of expression.Yield is 65%, purity 99.98%.Measure gainedization Compound1H NMR and mass spectrographic result and the determination data one for the method gained compound recorded using non-patent literature 1 Cause.
1H NMRδ5.86（M, 1H）, 5.46（D, 1H）, 5.28（D, 1H）, 3.29（D, 1H）, 2.44（S, 1H）, 1.51（S, 1H）, 1.44（S, 3H）, 1.33（S, 3H）ppm.
LRMS（EI）M/z173,157,141,83,69.
（Comparative example 10）The preparation method that non-patent literature 1 is recorded
The method recorded by non-patent literature 1 is manufactured by formula（I-7-1）The compound of expression.
In the reaction vessel with agitating device, thermometer and dripping device, to by formula（I-7-1）The chemical combination of expression Thing 14g（75.2 mMs）Dichloromethane solution 50mL drip while ice cooling triethylamine 21mL（150 mMs）With And methylchloroformate 11.6mL（150 mMs）.After when stirring 2 is small while ice cooling, solvent is distilled.By in diethyl Suspend, filter and be concentrated to give by formula in ether（I-7-2）The compound 16.4g of expression.Obtained by use by formula（I-7-2）Represent Compound 16.4g reduced by the method that non-patent literature 1 is recorded, obtain by formula（I-7）The compound of expression 7.03g.Yield is 54%, purity 99.34%.
（Embodiment 8）By formula（I-8）The compound of expression（The compound that patent document 2 is recorded）Manufacture
[chemical formula 14]
Patent document 2 record manufacture method in, except by 3,4- bis--（6- acryloxy hexyloxies）The four of benzoic acid The tetrahydrofuran solution 50mL of hydrogen tetrahydrofuran solution 50mL and diisopropylethylamine respectively from different dripping devices with（3,4- Two-（6- acryloxy hexyloxies）The solution of benzoic acid）：（Diisopropylethylamine solution）=1：1 speed of dripping is dripped at the same time In addition, manufactured by same method by formula（I-8）The compound of expression.Yield is 46%, purity 99.30%.Measure gained The IR spectrum of compound,1HNMR and mass spectrographic result and the measure number for the method gained compound recorded using patent document 2 According to consistent.
IR（KBr）2937,1717,1632,1598,1516,1495,1474,1410,1295,1265,1207,1189, 1160,1078,992,812,756cm-1.
1H NMRδ0.95（T, 3H）, 1.50-1.91（M, 18H）, 2.63（Q, 2H）, 4.08-4.21（M, 8H）, 5.82- 6.44（M, 8H）, 6.70（D, 1H）, 6.95（D, 1H）, 7.41-7.17（M, 4H）, 7.69（D, 1H）, 7.73（D, 1H）, 7.84- 8.23（M, 4H）, 8.82（S, 1H）ppm.LRMS（EI）m/z820（100）.
（Comparative example 11）The preparation method that patent document 2 is recorded
Below 0 DEG C, to the tetrahydrofuran solution of mesyl chloride drip 3,4- bis--（6- acryloxy hexyloxies）Benzene first The tetrahydrofuran solution of acid and diisopropylethylamine.After the completion of dripping, directly stir 30 minutes, by the 4- bis- that a spatula is micro The mixed solution of dimethylaminopyridine, diisopropylethylamine and tetrahydrofuran drips while remaining below -10 DEG C.Directly Tap into row 2 it is small when stirring after, reaction solution is washed with water, 1% hydrochloric acid and toluene is added, after water-oil separating, organic layer is washed with water Wash 2 times.Under reduced pressure, after distilling solvent, silica gel column chromatography is used（Developing solvent：Toluene）It is refined, carried out followed by methanol Reprecipitation, filters precipitate, manufactures by formula（I-8）The compound of expression.Yield is 26%, purity 99.31%.
（Embodiment 9）By formula（I-9）The compound of expression（The compound that patent document 1 is recorded）Manufacture
[chemical formula 15]
In the manufacture method that patent document 1 is recorded, except will be by formula（I-3-1）The tetrahydrofuran of the compound of expression is molten The tetrahydrofuran solution 100mL of liquid 300mL and triethylamine respectively from different dripping devices with（By formula（I-3-1）Represent The solution of compound）：（Triethylamine solution）=3：Beyond 1 speed of dripping is dripped at the same time, manufactured by same method by formula （I-9）The compound of expression.Yield is 82%, purity 99.35%.Measure gained compound1H NMR and mass spectrographic result The determination data of compound is consistent obtained by the method recorded as patent document 1.
1H NMR（CDCl3）δ8.70（S, 2H）, 8.49（S, 1H）, 8.18-8.11（M, 4H）, 7.93（D, 2H）, 7.40- 7.26（M, 4H）, 6.99（D, 4H）, 6.41（D, 2H）, 6.13（Dd, 2H）, 5.83（D, 2H）, 4.20-4.06（M, 8H）, 3.60 （S, 3H）, 1.85-1.70（M, 8H）, 1.57-1.20（M, 8H）ppm.
LRMS（EI）m/z846（100）.
（Comparative example 12）
With scale similarly to Example 9 by being manufactured with the same manufacture method of comparative example 1 by formula（I-9）The change of expression Compound.Yield is 72%, purity 99.31%.
（Embodiment 10）By formula（I-10）The compound of expression（The compound that EP0888281B1 publications are recorded）Manufacture
[chemical formula 16]
Modulated by method similarly to Example 3 by formula（I-3-2）The solution of the compound of expression.That is, with stirring Mix and mesyl chloride 5.00g is added in the reaction unit of device, thermometer and 2 dripping devices（43.6 mMs）And tetrahydrochysene Furans 10mL.Will be by formula while ice cooling（I-3-1）The compound 12.9g of expression（44.1 mMs）Tetrahydrofuran it is molten Liquid 60mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 30mL respectively from different dripping devices with（By Formula（I-3-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time.
Then, after when stirring 1 is small while ice cooling, 4-dimethylaminopyridine 0.54g is added（4.41 mM） And by formula（I-10-1）The compound 9.52g of expression（43.6 mMs）.By triethylamine 5.25g while ice cooling （51.9 mMs）Drip.Stir 3 it is small when after, distill solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.Will After organic layer brine It and neutralization, column chromatography is utilized（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, Obtain by formula（I-10）The compound 19.5g of expression.Yield is 91%, purity 99.43%.Measure gained compound1H NMR、13C NMR and mass spectrographic result and compound obtained by the method as the record of Japanese Unexamined Patent Application Publication 2000-507932 publications Determination data is consistent.
1H NMR（CDCl3）δ0.91（T, 3H）, 1.09（M, 2H）, 1.19-1.54（M, 12H）, 1.73（Quin, 2H）, 1.86（M, 6H）, 2.49（T, 1H）, 4.05（T, 2H）, 4.18（T, 2H）, 5.82（D, 1H）, 6.12（Dd, 1H）, 6.40（D, 1H）, 6.95（D, 2H）, 7.10（D, 2H）, 7.24（D, 2H）, 8.13（D, 2H）ppm.
13C NMR（CDCl3）δ 14.4,20.0,25.7,25.7,28.5,29.0,33.5,34.4,37.0,39.7,44.1, 64.4,68.0,114.2,121.3,121.8,127.7,128.5,130.5,132.2,145.2,148.9,163.3,165.1, 166.3ppm.
LRMS（EI）m/z492（100）.
（Comparative example 13）
With scale similarly to Example 10, except being blended with by formula（I-3-1）The compound and triethylamine of expression Tetrahydrofuran solution drip beyond, manufactured by method similarly to Example 10 by formula（I-10）The compound of expression.Receive Rate is 87%, purity 99.41%.
（Comparative example 14）The preparation method that EP0888281B1 publications are recorded
With scale similarly to Example 10, the method recorded by EP0888281B1 publications is manufactured by formula（I-10） The compound of expression.Yield is 70%, purity 99.01%.
（Embodiment 11）By formula（I-11）The compound of expression（The compound that EP1786887B1 publications are recorded）Manufacture
[chemical formula 17]
In embodiment 10, except will be by formula（I-10-1）The compound of expression is replaced with by formula（I-11-1）The change of expression Beyond compound, manufactured by method similarly to Example 10 by formula（I-11）The compound of expression.Yield is 87%, and purity is 99.41%.Measure gained compound1H NMR、13C NMR and mass spectrographic result by EP1786887B1 publications with being recorded Method obtained by compound determination data it is consistent.
1H NMR（CDCl3）δ1.51（M, 4H）, 1.73（Quin, 2H）, 1.85（Quin, 2H）, 3.84（S, 3H）, 4.06 （T, 2H）, 4.19（T, 2H）, 5.82（D, 1H）, 6.12（Dd, 1H）, 6.40（D, 1H）, 6.89（D, 2H）, 6.98（D, 2H）, 7.25（D, 1H）, 7.43（M, 3H）, 7.62（D, 1H）, 8.17（D, 2H）ppm.
13C NMR（CDCl3）δ 25.7,25.7,28.5,28.9,55.3,64.4,68.1,86.2,90.5,114.0, 114.4,114.7,120.7,122.6,123.9,127.1,128.5,130.5,130.7,132.5,132.9,133.1, 147.0,159.9,163.7,163.8,166.3ppm.
LRMS（EI）m/z532（100）.
（Comparative example 15）
With scale similarly to Example 11, except being blended with by formula（I-3-1）The compound and triethylamine of expression Tetrahydrofuran solution drip beyond, manufactured by method similarly to Example 11 by formula（I-11）The compound of expression.Receive Rate is 85%, purity 99.40%.
（Comparative example 16）The preparation method that EP1786887B1 publications are recorded
With scale similarly to Example 11, the method recorded by EP1786887B1 publications is manufactured by formula（I-11） The compound of expression.Yield is 65%, purity 98.60%.
（Embodiment 12）By formula（I-12）The compound of expression（Compound described in WO2009-060843 publications）'s Manufacture
[chemical formula 18]
Mesyl chloride 5.00g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （43.6 mMs）And dichloromethane 10mL.Will be by formula while ice cooling（I-12-1）The compound 5.72g of expression （43.6 mMs）Tetrahydrofuran solution 20mL and triethylamine 5.29g（52.3 mMs）Tetrahydrofuran solution 20mL points Not from different dripping devices with（By formula（I-12-1）The solution of the compound of expression）：（Triethylamine solution）=1：1 speed of dripping Degree drips at the same time.After being stirred 30 minutes while ice cooling, 4-dimethylaminopyridine 0.53g is added（4.3 mM）With And by formula（I-12-2）The compound 8.43g of expression（43.6 mMs）.By triethylamine 5.29g while ice cooling（52.3 MM）Drip.Stir 1 it is small when after, distill solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.Will be organic After layer brine It and neutralization, column chromatography is utilized（Silica gel）Refined, obtained by formula（I-12）The compound of expression 11.2g（42.2 mMs）.Yield is 84%, purity 99.93%.Measure gained compound1H NMR、13C NMR and matter The result of spectrum is consistent with the determination data of the compound as obtained by the method described in WO2009-060843 publications.
（Comparative example 17）
With scale similarly to Example 12, except being blended with by formula（I-12-1）The compound and triethylamine of expression Tetrahydrofuran solution drip beyond, manufactured by method similarly to Example 12 by formula（I-12）The compound of expression.Receive Rate is 82%, purity 99.90%.
（Embodiment 13）By formula（I-13）The compound of expression（Journal of the American Chemical Society, volume 131, p.3812-3813（2009）The compound of record）Manufacture
[chemical formula 19]
Mesyl chloride 7.50g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （65.5 mMs）And dichloromethane 10mL.Will be by formula while ice cooling（I-13-1）The compound 37.5g of expression （66.2 mMs）Dichloromethane solution 120mL and triethylamine 7.29g（72.1 mMs）Dichloromethane solution 60mL Respectively from different dripping devices with（By formula（I-13-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 drips Speed is dripped at the same time.After being stirred 30 minutes while ice cooling, 4-dimethylaminopyridine 0.80g is added（6.6 mM） And by formula（I-13-2）The compound 7.50g of expression（62.9 mMs）.By triethylamine 7.29g while ice cooling （72.1 mMs）Drip.Stir 1 it is small when after, distill solvent, utilize column chromatography（Silica gel）Refined, obtained by formula（I- 13）The compound 36.9g of expression.Yield is 88%, purity 99.91%.Measure gained compound1H NMR、13C NMR and Mass spectrographic result with by Journal of the American Chemical Society, volume 131, p.3812-3813 （2009）The determination data of compound is consistent obtained by the method for record.
1H NMR（C6D6）δ7.82（S, 1H）, 7.15（S, 1H）, 6.90（S, 1H）, 6.78（1H）, 6.69（Dd, 1H）, 5.82（D, 1H）, 5.65（Dd, 1H）, 4.22（M, 4H）, 4.16（D, 1H）, 3.24（M, 1H）, 3.14（M, 1H）, 3.12（S, 3H）, 3.02（S, 2H）, 2.80（M, 1H）, 2.66（M, 1H）, 1.49（S, 3H）, 1.47（S, 3H）, 0.94（M, 4H）, -0.07 （S, 9H）, -0.11（S, 9H）ppm.
13C NMR（C6D6）δ 201.1,169.3,154.1,153.7,152.6,141.7,140.5,139.8,130.5, 126.7,126.2,116.5,116.0,110.1,88.2,67.0,63.3,57.7,46.2,39.7,27.6,22.7,18.0, 17.6,16.4, -1.6, -1.7ppm.
LRMS（EI）m/z666（100）.
（Comparative example 18）
With scale similarly to Example 13, except being blended with by formula（I-13-1）The compound and triethylamine of expression Dichloromethane solution drip beyond, manufactured by method similarly to Example 13 by formula（I-13）The compound of expression.Receive Rate is 85%, purity 99.88%.
（Embodiment 14）By formula（I-14）The manufacture of the compound of expression
[chemical formula 12]
6-Hydroxy-2-naphthoic acid is added in the reaction vessel with agitating device, cooler and thermometer（By formula （I-14-1）The compound of expression）100g（0.53 mole）, acetic acid 300mL, acetic anhydride 65.1g（0.64 mole）, sulfuric acid 5g, add Heat is to 60 DEG C, when reaction 8 is small.In reaction solution add water 1L, while ice cooling stir 1 it is small when after, to the solid of precipitation Filtered.The solid of gained is carried out twice dispersing with water 1L to wash.By drying solid, obtain by formula（I-14-2）Table The compound 118 .7g shown.
Mesyl chloride 5.00g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （43.6 mMs）And tetrahydrofuran 10mL.Will be by formula while ice cooling（I-14-2）The compound 10.2g of expression （44.1 mMs）Tetrahydrofuran solution 50mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 25mL points Not from different dripping devices with（The solution of 4-ABA）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time Under.After being stirred 30 minutes while ice cooling, 4-dimethylaminopyridine 0.53g is added（4.3 mM）And 2,4- bis- Methylphenol 5.32g（43.6 mMs）.By triethylamine 5.25g while ice cooling（51.9 mMs）Drip.It is small to stir 1 Shi Hou, distills solvent, adds dichloromethane and 5% hydrochloric acid carries out liquid separation processing.By organic layer brine It and neutralize Afterwards, column chromatography is utilized（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-14-4）The change of expression Compound 14.1g（42.2 mMs）.Yield is 97%, purity 99.57%.
Added in the reaction vessel with agitating device and dripping device by formula（I-14-4）The compound of expression 14.1g（42.2 mMs）, dissolved in toluene 30mL and tetrahydrofuran 30mL.By butylamine 4.62g（63.3 mMs）Drop Under, be stirred at room temperature 7 it is small when.After carrying out liquid separation and carrying out washing treatment with 5% hydrochloric acid and saline solution, pass through recrystallization（First Alcohol/water）Refined, obtained by formula（I-14-5）The compound 12.1g of expression（41.3 mMs）.
Mesyl chloride 4.73g is added in the reaction vessel with agitating device, thermometer and 2 dripping devices （41.3 mMs）And tetrahydrofuran 10mL.Will be by formula while ice cooling（I-14-6）The compound 10.3g of expression （41.3 mMs）Tetrahydrofuran solution 50mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 25mL points Not from different dripping devices with（The solution of 4-ABA）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time Under.After being stirred 30 minutes while ice cooling, 4-dimethylaminopyridine 0.53g is added（4.3 mM）And by formula（I- 14-5）The compound 12.1g of expression（41.3 mMs）.By triethylamine 5.25g while ice cooling（51.9 mMs）Drop Under.Stir 1 it is small when after, distill solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.By organic layer saline solution After washing and neutralizing, column chromatography is utilized（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained by formula（I-14） The compound 20.8g of expression（39.6 mMs）.Yield is 96%, purity 99.68%.
1H NMR（CDCl3）δ 2.20~2.26（M, 5H）, 2.35（S, 3H）, 4.18（T, 2H）, 4.40（T, 2H）, 5.85 （Dd, 1H）, 6.14（Dd, 1H）, 6.43（Dd, 1H）, 7.01（D, 2H）, 7.07（S, 2H）, 7.11（S, 1H）, 7.46（Dd, 1H）, 7.77（D, 1H）, 7.93（D, 1H）, 8.06（D, 1H）, 8.20（D, 2H）, 8.24（Dd, 1H）, 8.82（D, 1H）ppm.
13C NMR（CDCl3）δ 16.2,20.8,28.5,61.1,64.7,114.3,118.8,121.6,121.6,122.5, 126.2,126.6,127.5,128.1,128.2,129.8,130.4,131.0,131.6,131.8,132.4,135.7, 136.4,147.3,150.8,163.2,164.7,165.0,166.1ppm.
LRMS（EI）m/z524（100）.
（Comparative example 19）
With reaction scale similarly to Example 14, will only obtain by formula（I-14-4）The process of the compound of expression, with And obtain by formula（I-14）The Adding Way of reagent is changed to the tetrahydrofuran to mesyl chloride in the process of the compound of expression Solution drips the method for the tetrahydrofuran solution for being mixed with triethylamine and carboxylic acid, manufactures by formula（I-14）The compound of expression. Gained compound, yield 95%, purity 98.57%, and yield are 92% in each process, purity 99.37%.
（Embodiment 15）By formula（I-14）The manufacture of the compound of expression
[chemical formula 12]
Modulated by method similarly to Example 3 by formula（I-3-2）The solution of the compound of expression.That is, with stirring Mix and mesyl chloride 5.00g is added in the reaction unit of device, thermometer and 2 dripping devices（43.6 mMs）And tetrahydrochysene Furans 10mL.Will be by formula while ice cooling（I-3-1）The compound 12.9g of expression（44.1 mMs）Tetrahydrofuran it is molten Liquid 60mL and triethylamine 5.25g（51.9 mMs）Tetrahydrofuran solution 30mL respectively from different dripping devices with（By Formula（I-3-1）The solution of the compound of expression）：（Triethylamine solution）=2：1 speed of dripping is dripped at the same time.
Then, after when stirring 1 is small while ice cooling, 4-dimethylaminopyridine 0.54g is added（4.41 mM） And by formula（I-6-3）The compound 10.6g of expression（43.6 mMs）.By triethylamine 5.25g while ice cooling（51.9 MM）Drip.Stir 3 it is small when after, distill solvent, add dichloromethane and 5% hydrochloric acid carries out liquid separation processing.Will be organic After layer brine It and neutralization, column chromatography is utilized（Silica gel）And reprecipitation（Methylene chloride/methanol）Refined, obtained By formula（I-15）The compound 21.6g of expression.Yield is 96%, purity 99.55%.
1H NMR（CDCl3）δ 1.45~1.57（M, 4H）, 1.73（Quin, 2H）, 1.85（Quin, 2H）, 2.19（S, 3H）, 2.34（S, 3H）, 4.06（T, 2H）, 4.18（T, 2H）, 5.82（Dd, 1H）, 6.12（Dd, 1H）, 6.41（Dd, 1H）, 6.97~ 7.08（M, 5H）, 7.36（D, 2H）, 8.15（D, 2H）, 8.29（D, 2H）ppm.
13C NMR（CDCl3）δ 16.1,20.8,25.6,25.7,28.5,28.9,64.4,68.1,114.3,121.0, 121.6,122.0,126.9,127.2,127.5,128.5,129.8,130.5,131.7,131.8,132.4,135.6, 147.2,155.2,163.7,164.3,164.3,166.3ppm.
LRMS（EI）m/z516（100）.
（Comparative example 20）
With scale similarly to Example 15, except being blended with by formula（I-3-1）The compound and triethylamine of expression Tetrahydrofuran solution drip beyond, manufactured by method similarly to Example 15 by formula（I-15）The compound of expression.Receive Rate is 88%, purity 99.43%.
（Embodiment 16~25 and comparative example 21~33）The evaluation of film
Modulation is by following compounds（A）30%th, compound（B）40% and compound（C）The precursor compositions of 30% composition （M）.
[chemical formula 18]
Adjustment contains precursor compositions（M）67.9%th, manufactured by the manufacturing method of the present invention and known manufacture method By formula（I-3）, formula（I-4）, formula（I-5）, formula（I-6）, formula（I-8）, formula（I-9）, formula（I-10）And formula（I-11）Represent Compound each 29.1% and Photoepolymerizationinitiater initiater Irgacure907（Ciba Specialty Chemicals' system）3% polymerizable composition, polymerizable composition （N）.By the polymerizable composition, polymerizable composition（N）Cyclopentanone solution（Polymerizable composition, polymerizable composition（N）Concentration 25%）In the band of ground processing Have and be coated on the glass of polyimides with spin-coating method, it is 3 minutes dry at 65 DEG C.The film of gained is placed in 60 DEG C of heat On plate, with 20mW/cm2Intensity illumination ultraviolet 60 seconds.Evaluate the appearance and yellow colour index of resulting polymers（YI）.It is if logical Crossing on visual polymer does not have then to be denoted as ◎ if mottled grade, entirety are homogeneous, and somewhat visible mottled situation is denoted as △, it is seen that compared with More mottled situation is denoted as ×.In addition, yellow colour index is surveyed using JASCO UV/VIS Spectrophotometer V-560 Determine the absorption spectrum of polymer, and yellowing is calculated with attached color diagnostic program（YI）.YI by
YI=100（1.28X-1.06Z）/Y（JIS K7373）
Calculate.
Then, the polymer of gained is dried 60 minutes afterwards at 200 DEG C.Above formula is similarly utilized for the YI after rear baking Calculate.
In addition, on compound（I-9）, since yellow is presented in compound in itself, without the measure for carrying out YI.Separately Outside, the compound of manufacture is have studied in comparative example 5（I-3）Since reaction yield is low, separation is difficult, do not evaluated.Will The results are shown in following table.
[table 3]
Polymer The manufacture method of compound Evaluate compound It is mottled YI YI after drying afterwards
Embodiment 16 Embodiment 3 Compound（I-3） ◎ 0.5 0.7
Embodiment 17 Embodiment 4 Compound（I-4） ◎ 1.0 1.4
Embodiment 18 Embodiment 5 Compound（I-5） ◎ 0.4 0.8
Embodiment 19 Embodiment 6 Compound（I-6） ◎ 1.2 2.6
Embodiment 20 Embodiment 8 Compound（I-8） ◎ 0.8 2.5
Embodiment 21 Embodiment 9 Compound（I-9） ◎ - -
Embodiment 22 Embodiment 10 Compound（I-10） ◎ 1.4 5.5
Embodiment 23 Embodiment 11 Compound（I-11） ◎ 0.4 0.9
Embodiment 24 Embodiment 14 Compound（I-14） ◎ 1.3 5.3
Embodiment 25 Embodiment 15 Compound（I-15） ◎ 1.4 5.6
Comparative example 21 Comparative example 3 Compound（I-3） × 1.5 6.5
Comparative example 22 Comparative example 4 Compound（I-3） × 2.6 8.6
Comparative example 23 Comparative example 5 Compound（I-3） - - -
Comparative example 24 Comparative example 6 Compound（I-3） × 0.5 2.7
Comparative example 25 Comparative example 7 Compound（I-4） △ 1.6 2.3
Comparative example 26 Comparative example 8 Compound（I-5） × 0.5 1.5
Comparative example 27 Comparative example 9 Compound（I-6） △ 1.7 5.4
Comparative example 28 Comparative example 11 Compound（I-8） × 2.7 6.7
Comparative example 29 Comparative example 12 Compound（I-9） × - -
Comparative example 30 Comparative example 13 Compound（I-10） △ 2.3 8.8
Comparative example 31 Comparative example 14 Compound（I-10） △ 0.9 2.4
Comparative example 32 Comparative example 15 Compound（I-11） △ 2.2 8.6
Comparative example 33 Comparative example 16 Compound（I-11） △ 1.0 6.9
Comparative example 32 Comparative example 19 Compound（I-14） △ 2.2 8.6
Comparative example 33 Comparative example 20 Compound（I-15） △ 1.5 7.9
As described above, the manufacturing method of the present invention can obtain target compound in high yield.In addition, it is thus identified that during manufacture The impurity content of generation is few.Can be produced when polymer is made using it if impurity content increases it is mottled, and YI be deteriorated.Can Know there is no spot using the polymer made containing the polymerizable liquid crystal compound of compound obtained by the application manufacture method Refute, the yellow colour index after polymerization and after rear baking is very low value, i.e. almost without discoloration is caused.Therefore, the present invention is passed through Manufacture method manufacture compound be particularly it is useful in the purposes of film.

Claims (1)

  1. A kind of 1. manufacture method of ester compounds (6), it is characterised in that not by the compound (1) with least one carboxyl and Alkali (2) is pre-mixed but is added at the same time to acetyl halide compound (3), is reacted and mixed acid anhydride (4) is made, then make to have The compound (5) of at least one group selected from hydroxyl and/or sulfydryl is further reacted,
    The acetyl halide compound (3) is the compound represented by following formula (III-1) or formula (III-2),
    In formula, U1Represent methyl, tolyl, U2Representing methoxyl group, ethyoxyl and methyl, V represents halogen,
    The compound (1) with least one carboxyl is the compound represented by the following general formula (I),
    R1——G1——W1 (I)
    In formula (I), G1Represent following formula (i),
    In formula (i), A1Isosorbide-5-Nitrae-phenylene, naphthalene -2,6- diyl, Isosorbide-5-Nitrae-cyclohexylidene, 1,3- dioxane -2 are represented independently of one another, 5- diyls, these groups can be unsubstituted or be taken independently of one another by the alkyl of halogen, cyano group, nitro or carbon number 1 to 10 Generation, 1-CH on the alkyl2- or non-conterminous more than 2-CH2- can be independently of one another by-O- ,-CO- ,-COO- ,-OCO- Substitution,
    Z11And Z12Expression-O- ,-OCH independently of one another2-、-CH2O-、-COO-、-OCO-、-CH2CH2- ,-CH=CH- COO- ,-OCO-CH=CH- ,-COO-CH2CH2-、-OCO-CH2CH2-、-CH2CH2-COO-、-CH2CH2- OCO- ,-CY=CY- ,- The alkylidene or singly-bound of C ≡ C-, carbon number 1 to 20, in formula, Y represents hydrogen atom, carbon number 1 to 12 independently of one another Alkyl, more than 1 hydrogen atom can be replaced by fluorine atoms independently of one another in the alkylidene, and m11 represents 1 to 8 integer,
    R1And W1Hydrogen atom, fluorine atom, the alkyl or P-Sp- of carbon number 1 to 12 are represented independently of one another, 1 in the alkyl Above hydrogen atom can be replaced by fluorine atoms independently of one another,
    In formula, P represents to be selected from following formulas (P-1) to (P-3),
    Sp represents 1-CH2- or non-conterminous more than 2-CH2- the carbon that can be substituted independently of one another by-O- ,-COO- ,-OCO- The alkylidene or singly-bound of atomicity 1 to 20, can be that identical group can also be different groups, R1And W1In at least One expression carboxyl,
    Alkali (2) is tertiary amine or aromatic amine and its amine salt,
    Compound (5) with least one group selected from hydroxyl and/or sulfydryl is to be represented by the following general formula (II) Compound,
    R2——G2——W2 (II)
    In formula (II), G2Represent following formula (ii),
    In formula (ii), A2Isosorbide-5-Nitrae-phenylene, naphthalene -2,6- diyl, Isosorbide-5-Nitrae-cyclohexylidene, 1,3- dioxane -2 are represented independently of one another, 5- diyls or singly-bound, these groups can be unsubstituted or independently of one another by halogen, cyano group, nitro or carbon numbers 1 to 10 Alkyl substitutes, 1-CH on the alkyl2- or non-conterminous more than 2-CH2- can independently of one another by-O- ,-CO- ,- COO- ,-OCO- substitute, Z21And Z22Expression-O- ,-OCH independently of one another2-、-CH2O-、-COO-、-OCO-、-CH2CH2-、- CH=CH-COO- ,-OCO-CH=CH- ,-COO-CH2CH2-、-OCO-CH2CH2-、-CH2CH2-COO-、-CH2CH2-OCO-、-CY The alkylidene or singly-bound of=CY- ,-C ≡ C-, carbon number 1 to 20, in formula, Y represents hydrogen atom, carbon number 1 independently of one another To 12 alkyl, more than 1 hydrogen atom can be replaced by fluorine atoms independently of one another in the alkylidene, and m21 represents 0 to 8 integer,
    R2And W2Hydrogen atom, fluorine atom, the alkyl or P-Sp- of carbon number 1 to 12 are represented independently of one another, 1 in the alkyl Above hydrogen atom can be replaced by fluorine atoms independently of one another, and in formula, P represents the implication identical with leading to the P in formula (I), and Sp is represented The implication identical with the Sp in logical formula (I), can be that identical group can also be different groups, R2And W2In at least One group for representing to select from hydroxyl and/or sulfydryl.
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